The immune mechanisms responsible for killing of CMV-infected targets and the importance of such mechanisms for recovery from CMV infections will be investigated. The role of interferon (IFN) in natural killing (NK) of CMV-infected targets will be further defined. The IFN produced by mononuclear cells exposed to CMV-infected target cells will be characterized by pH stability and neutralization assays. The ability of IFN- Alpha and IFN- Lambda to stimulate NK cells and to protect CMV-infected and uninfected target cells from lysis will be determined. We will determine whether HLA-restricted T-lymphocyte killing of CMV targets can be detected. Effector cells from individuals receiving CMV vaccine and from renal transplant recipients will be tested for T-lymphocyte cytotoxicity against CMV-infected syngeneic fibroblasts prepared from their own skin biopsies. Young adults with CMV mononucleosis will be tested for cytotoxic activity against partially HLA-matched and unmatched CMV-infected targets. The clinical importance of NK and T-lymphocyte cytotoxicity against CMV targets will be determined by a prospective study in renal transplant recipients. Virological and immunological studies including CMV serology, CMV-specific lymphocyte proliferation IFN production, and cytotoxicity against CMV-infected targets will be obtained at specified intervals post-transplantation. Factors which influence the risk of CMV disease such as donor and recipient CMV serology, immunosuppressive therapy and the source of the donor kidney will be correlated with immunological results and clinical events. The temporal relationships between CMV disease and immune responses will be determined for each individual. The cells responsible for cytotoxic activity in renal transplant recipients with CMV disease will be further defined. The results of this study may provide information on immune deficits contributing to severe CMV disease. Once such mechanisms are understood it may be possible to decrease the incidence of CMV disease by monitoring immunosuppressive therapy or by using immunostimulants, such as IFN.